Related Experiment Video
Updated: Aug 16, 2026
Neutrophil Isolation and Analysis to Determine their Role in Lymphoma Cell Sensitivity to Therapeutic Agents
Published on: March 25, 2016
Vincristine resistance development in lymphoblastoid cells under conditions of selective P-glycoprotein inhibition
Arcadi Svirnovski1, Vadim Pasiukov, Sergei Grigorovich
1Laboratory for Molecular Genetics Investigations in Leukemia and Blood Disorders, Republican Research and Practical Center for Hematology and Transfusiology, Ministry of Health, 160 Dolginovski Tract, Minsk 223-059, Belarus. svirnov@users.med.by
Abstract:
Most studies looking at the reversal of drug resistance in hematological malignancies have focused on the blockade of P-glycoprotein (Pgp) pump activity, as one of the more important proteins involved in cell resistance to the chemotherapeutic agents used. In model experiments using the IM-9 lymphoblastoid cell line cultured with increasing doses of vincristine (Vcr) in the presence or absence of the Pgp blocker cyclosporin A (CsA) we established two Vcr resistant sublines. By measuring Pgp expression in target cells, and the activity and sensitivity to cytostatics we believe that our results suggest the presence of other mechanisms involved in cell resistance to xenobiotics and that these mechanisms should be considered in the development of clinical trials designed to overcome drug resistance.
Insights
This study investigated drug resistance in blood cancers, finding that blocking P-glycoprotein (Pgp) alone isn't enough. Other resistance mechanisms exist and must be considered for effective cancer treatments.
Area of Science:
- Hematology
- Pharmacology
- Molecular Biology
Background:
- Drug resistance in hematological malignancies is a major challenge in cancer therapy.
- P-glycoprotein (Pgp) is a key protein involved in multidrug resistance (MDR).
- Current strategies often focus on inhibiting Pgp activity to reverse drug resistance.
Purpose of the Study:
- To investigate mechanisms of vincristine (Vcr) resistance in hematological cell lines.
- To evaluate the role of P-glycoprotein (Pgp) blockade in overcoming Vcr resistance.
- To identify potential alternative mechanisms contributing to drug resistance.
Main Methods:
- Established two Vcr-resistant IM-9 lymphoblastoid cell sublines.
- Cultured cells with increasing doses of Vcr, with and without cyclosporin A (CsA).
- Measured Pgp expression, Pgp pump activity, and cellular sensitivity to cytostatics.
Main Results:
- Vcr-resistant sublines were successfully established.
- Pgp blockade with CsA showed limited efficacy in reversing Vcr resistance.
- Results suggest the involvement of additional mechanisms beyond Pgp in conferring drug resistance.
Conclusions:
- Pgp blockade alone may not be sufficient to overcome drug resistance in hematological malignancies.
- Other xenobiotic resistance mechanisms should be investigated.
- These findings have implications for designing future clinical trials to combat drug resistance.
More Related Videos
08:52Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
Published on: May 27, 2011
07:17Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
Published on: June 22, 2016